Target-Enhanced Whole-Genome Sequencing (TE-WGS) Shows Clinical Validity Equivalent to Commercially Available Targeted Oncology Panel.

Purpose: Cancer poses a significant global health challenge, demanding precise genomic testing for individualized treatment strategies. Targeted-panel sequencing (TPS) has improved personalized oncology but often lacks comprehensive coverage of crucial cancer alterations. Whole-genome sequencing (WGS) addresses this gap, offering extensive genomic testing.

Quantitative and qualitative mutational impact of ionizing radiation on normal cells.

The comprehensive genomic impact of ionizing radiation (IR), a carcinogen, on healthy somatic cells remains unclear. Using large-scale whole-genome sequencing (WGS) of clones expanded from irradiated murine and human single cells, we revealed that IR induces a characteristic spectrum of short insertions or deletions (indels) and structural variations (SVs), including balanced inversions, translocations, composite SVs (deletion-insertion, deletion-inversion, and deletion-translocation composites), and complex genomic rearrangements (CGRs), including chromoplexy, chromothripsis, and SV by breakage-fusion-bridge cycles. Our findings suggest that 1 Gy IR exposure causes an average of 2.

Comprehensive characterization of maternal, fetal, and neonatal microbiomes supports prenatal colonization of the gastrointestinal tract.

In this study, we aimed to comprehensively characterize the microbiomes of various samples from pregnant women and their neonates, and to explore the similarities and associations between mother-neonate pairs, sample collection sites, and obstetrical factors. We collected samples from vaginal discharge and amniotic fluid in pregnant women and umbilical cord blood, gastric liquid, and meconium from neonates. We identified 19,597,239 bacterial sequences from 641 samples of 141 pregnant women and 178 neonates.

ClinPharmSeq: A targeted sequencing panel for clinical pharmacogenetics implementation.

The accurate identification of genetic variants contributing to therapeutic drug response or adverse effects is the first step in implementation of precision drug therapy. Targeted sequencing has recently become a common methodology for large-scale studies of genetic variation thanks to its favorable balance between low cost, high throughput, and deep coverage. Here, we present ClinPharmSeq, a targeted sequencing panel of 59 genes with associations to pharmacogenetic (PGx) phenotypes, as a platform to explore the relationship between drug response and genetic variation, both common and rare.

Indigenous Ancestry and Admixture in the Uruguayan Population.

The Amerindian group known as the Charrúas inhabited Uruguay at the timing of European colonial contact. Even though they were extinguished as an ethnic group as a result of a genocide, Charrúan heritage is part of the Uruguayan identity both culturally and genetically. While mitochondrial DNA studies have shown evidence of Amerindian ancestry in living Uruguayans, here we undertake whole-genome sequencing of 10 Uruguayan individuals with self-declared Charruan heritage.

Genomic and transcriptomic analyses reveal a tandem amplification unit of 11 genes and mutations in mismatch repair genes in methotrexate-resistant HT-29 cells.

DHFR gene amplification is commonly present in methotrexate (MTX)-resistant colon cancer cells and acute lymphoblastic leukemia. In this study, we proposed an integrative framework to characterize the amplified region by using a combination of single-molecule real-time sequencing, next-generation optical mapping, and chromosome conformation capture (Hi-C). We identified an amplification unit spanning 11 genes, from the DHFR gene to the ATP6AP1L gene position, with high adjusted interaction frequencies on chromosome 5 (~2.

Evaluation of low-pass genome sequencing in polygenic risk score calculation for Parkinson's disease.

Background: Low-pass sequencing (LPS) has been extensively investigated for applicability to various genetic studies due to its advantages over genotype array data including cost-effectiveness. Predicting the risk of complex diseases such as Parkinson's disease (PD) using polygenic risk score (PRS) based on the genetic variations has shown decent prediction accuracy. Although ultra-LPS has been shown to be effective in PRS calculation, array data has been favored to the majority of PRS analysis, especially for PD.

Classification of High-Grade Serous Ovarian Carcinoma by Epithelial-to-Mesenchymal Transition Signature and Homologous Recombination Repair Genes.

High-grade serous ovarian cancer (HGSOC) is one of the deadliest cancers that can occur in women. This study aimed to investigate the molecular characteristics of HGSOC through integrative analysis of multi-omics data. We used fresh-frozen, chemotherapy-naïve primary ovarian cancer tissues and matched blood samples of HGSOC patients and conducted next-generation whole-exome sequencing (WES) and RNA sequencing (RNA-seq).

Direct conversion of adult human fibroblasts into functional endothelial cells using defined factors.

We aimed to directly convert adult human dermal fibroblasts (aHDFs) into functional endothelial cells (ECs). Lentiviral vectors encoding endothelial transcription factors (TFs) were constructed. We examined whether five TFs (FOXO1, ER71, KLF2, TAL1, and LMO2) used for the generation of mouse induced ECs (iECs) could convert the aHDFs into human iECs.

The tumor immune microenvironmental analysis of 2,033 transcriptomes across 7 cancer types.

Understanding the tumor microenvironment is important to efficiently identify appropriate patients for immunotherapies in a variety of cancers. Here, we presented the tumor microenvironmental analysis of 2,033 cancer samples across 7 cancer types: colon adenocarcinoma, skin cutaneous melanoma, kidney renal papillary cell carcinoma, sarcoma, pancreatic adenocarcinoma, glioblastoma multiforme, and pheochromocytoma / paraganglioma from The Cancer Genome Atlas cohort. Unsupervised hierarchical clustering based on the gene expression profiles separated the cancer samples into two distinct clusters, and characterized those into immune-competent and immune-deficient subtypes using the estimated abundances of infiltrated immune and stromal cells.

Alterations of transcriptome signatures in head trauma-related neurodegenerative disorders.

Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease that is associated with repetitive traumatic brain injury (TBI). CTE is known to share similar neuropathological features with Alzheimer's disease (AD), but little is known about the molecular properties in CTE. To better understand the neuropathological mechanism of TBI-related disorders, we conducted transcriptome sequencing analysis of CTE including AD and CTE with AD (CTE/AD) post-mortem human brain samples.

Epigenome signatures landscaped by histone H3K9me3 are associated with the synaptic dysfunction in Alzheimer's disease.

The pathogenesis of Alzheimer's disease (AD) and the commonest cause of dementia in the elderly remain incompletely understood. Recently, epigenetic modifications have been shown to play a potential role in neurodegeneration, but the specific involvement of epigenetic signatures landscaped by heterochromatin has not been studied in AD. Herein, we discovered that H3K9me3-mediated heterochromatin condensation is elevated in the cortex of sporadic AD postmortem brains.

NARD: whole-genome reference panel of 1779 Northeast Asians improves imputation accuracy of rare and low-frequency variants.

Here, we present the Northeast Asian Reference Database (NARD), including whole-genome sequencing data of 1779 individuals from Korea, Mongolia, Japan, China, and Hong Kong. NARD provides the genetic diversity of Korean (n = 850) and Mongolian (n = 384) ancestries that were not present in the 1000 Genomes Project Phase 3 (1KGP3). We combined and re-phased the genotypes from NARD and 1KGP3 to construct a union set of haplotypes.

Integrative analysis of genomic and transcriptomic characteristics associated with progression of aggressive thyroid cancer.

Anaplastic thyroid cancer (ATC) and advanced differentiated thyroid cancers (DTCs) show fatal outcomes, unlike DTCs. Here, we demonstrate mutational landscape of 27 ATCs and 86 advanced DTCs by massively-parallel DNA sequencing, and transcriptome of 13 ATCs and 12 advanced DTCs were profiled by RNA sequencing. TERT, AKT1, PIK3CA, and EIF1AX were frequently co-mutated with driver genes (BRAF and RAS) in advanced DTCs as well as ATC, but tumor suppressors (e.

Comprehensive analysis of the tumor immune micro-environment in non-small cell lung cancer for efficacy of checkpoint inhibitor.

Characterizing the molecular immune subtype and micro-environment of lung cancer is necessary to understand immunogenic interactions between infiltrating immune and stromal cells, and how tumor cells overcome immune checkpoint blockades. This study seeks to identify computational methodologies for subtyping gene expression-based tumor-immune micro-environment interactions, which differentiate non-small cell lung cancer (NSCLC) into immune-defective and immune-competent subtypes. Here, 101 lung squamous cell carcinomas (LUSCs) and 87 lung adenocarcinomas (LUADs) tumor samples have been analyzed.

Peroxiredoxin5 Controls Vertebrate Ciliogenesis by Modulating Mitochondrial Reactive Oxygen Species.

Aims: Peroxiredoxin5 (Prdx5), a thioredoxin peroxidase, is an antioxidant enzyme that is widely studied for its antioxidant properties and protective roles in neurological and cardiovascular disorders. This study is aimed at investigating the functional significance of Prdx5 in mitochondria and at analyzing its roles in ciliogenesis during the process of vertebrate development.

Results: We found that several Prdx genes were strongly expressed in multiciliated cells in developing Xenopus embryos, and their peroxidatic functions were crucial for normal cilia development.

Development of a common platform for the noninvasive prenatal diagnosis of X-linked diseases.

Objective: The aim of this study was to develop a common targeted massively parallel sequencing platform for the noninvasive prenatal diagnosis (NIPD) of multiple X-linked diseases.

Method: The custom capture probe was designed to target 33 genes and recombination hotspots. We tested the carrier mother and male proband pair of 6 families.

Integrative analysis of oncogenic fusion genes and their functional impact in colorectal cancer.

Background: Fusion genes are good candidates of molecular targets for cancer therapy. However, there is insufficient research on the clinical implications and functional characteristics of fusion genes in colorectal cancer (CRC).

Methods: In this study, we analysed RNA sequencing data of CRC patients (147 tumour and 47 matched normal tissues) to identify oncogenic fusion genes and evaluated their role in CRC.

Targeted linked-read sequencing for direct haplotype phasing of maternal DMD alleles: a practical and reliable method for noninvasive prenatal diagnosis.

For the noninvasive prenatal diagnosis (NIPD) of X-linked recessive diseases such as Duchenne muscular dystrophy (DMD), maternal haplotype phasing is a critical step for dosage analysis of the inherited allele. Until recently, the proband-based indirect haplotyping method has been preferred despite its limitations for use in clinical practice. Here, we describe a method for directly determining the maternal haplotype without requiring the proband's DNA in DMD families.

Correction to: Identification of novel mutations in FFPE lung adenocarcinomas using DEPArray sorting technology and next-generation sequencing.

In the original article, part of Table 1 headings and entries were missing. The correct Table is as shown below. The original article has been corrected.

Whole Exome and Transcriptome Analyses Integrated with Microenvironmental Immune Signatures of Lung Squamous Cell Carcinoma.

The immune microenvironment in lung squamous cell carcinoma (LUSC) is not well understood, with interactions between the host immune system and the tumor, as well as the molecular pathogenesis of LUSC, awaiting better characterization. To date, no molecularly targeted agents have been developed for LUSC treatment. Identification of predictive and prognostic biomarkers for LUSC could help optimize therapy decisions.

Identification of novel mutations in FFPE lung adenocarcinomas using DEPArray sorting technology and next-generation sequencing.

Formalin-fixed paraffin-embedded (FFPE) tissues are utilized as the standard diagnostic method in pathology laboratories. However, admixture of unwanted tissues and shortage of normal samples, which can be used to detect somatic mutation, are considered critical factors to accurately diagnose cancer. To explore these challenges, we sorted the pure tumor cells from 22 FFPE lung adenocarcinoma tissues via Di-Electro-Phoretic Array (DEPArray) technology, a new cell sorting technology, and analyzed the variants with next-generation sequencing (NGS) for the most accurate analysis.